Gene-By-Environment Interactions in Urban Populations Modulate Risk Phenotypes
ARTICLE DOI: 10.1038/s41467-018-03202-2 OPEN Gene-by-environment interactions in urban populations modulate risk phenotypes Marie-Julie Favé1,2, Fabien C. Lamaze1, David Soave1, Alan Hodgkinson2,3, Héloïse Gauvin2,4, Vanessa Bruat1,2, Jean-Christophe Grenier 1,2, Elias Gbeha1, Kimberly Skead1, Audrey Smargiassi5, Markey Johnson6, Youssef Idaghdour7 & Philip Awadalla1,2,8,9 Uncovering the interaction between genomes and the environment is a principal challenge of 1234567890():,; modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to compre- hensively assess the interactions between 1.6 million data points, encompassing a range of environmental exposures, health, and gene expression levels, coupled with whole-genome genetic variation. From ∼1000 individuals of a founder population in Quebec, we reveal a substantial impact of the environment on the transcriptome and clinical endophenotypes, overpowering that of genetic ancestry. Air pollution impacts gene expression and pathways affecting cardio-metabolic and respiratory traits, when controlling for genetic ancestry. Finally, we capture four expression quantitative trait loci that interact with the environment (air pollution). Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual’s response to environmental challenges. 1 Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. 2 Sainte-Justine Research Center, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1C5, Canada. 3 Department of Medical and Molecular Genetics, Guy’s Hospital, King’s College London, London, WC2R 2LS, UK.
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